This is a proposal to investigate the hypothesis that an autoimmune process directed against brain tissue antigens might be causally related to the production of psychotic symptoms in schizophrenics. The plan to test this hypothesis is characterized by two approaches: 1) a cross-sectional study of multiple immunologic parameters in acutely psychotic schizophrenic patients, psychotic patients with Systemic Lupus Erythematosus (SLE) contrasted with schizophrenics in remission, previously unmedicated schizophrenics, nonpsychotic SLE patients, brain damaged non-psychotic patients and normal controls. This part of the investigation will show if there is a specific association between psychotic symptoms and an autoimmune anti-brain response. 2) A longitudinal follow up of the schizophrenic patients will then be carried out with frequent repeated measurements of immunologic parameters and of the level of psychotic symptomatology. This part of the investigation will reveal if the autoimmune phenomena and the level of psychotic symptoms covary and whether the autoimmune phenomena emerge before corresponding changes in clinical state. The design of the study has been derived from current models of immunopathophysiology in known autoimmune disorders such as SLE, Insulin Dependent Diabetes Mellitus and autoimmune hyperthyroidism. This study promises to answer in a definitive way questions raised by pilot data gathered by the Principal Investigator and by other studies over the last 30 years which have demonstrated an association between immune dysfunction and schizophrenia. Uncovering an autoimmune pathogenesis in even a subgroup of schizophrenics would lead to further studies of etiology in schizophrenia and also open the door to a number of novel treatment approaches based on modifying the immune response.